Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression

Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n=13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n=11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry. Our EEG asymmetry results suggest that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients, and that alpha-asymmetry EEG-nf would be compatible with the amygdala rtfMRI-nf. Combination of the two could enhance emotion regulation training and benefit MDD patients.Comment: 28 pages, 16 figures, to appear in NeuroImage: Clinica

Challenges in Multimodal Data Fusion

International audienceIn various disciplines, information about the same phenomenon can be acquired from different types of detectors, at different conditions, different observations times, in multiple experiments or subjects, etc. We use the term "modality" to denote each such type of acquisition framework. Due to the rich characteristics of natural phenomena, as well as of the environments in which they occur, it is rare that a single modality can provide complete knowledge of the phenomenon of interest. The increasing availability of several modalities at once introduces new degrees of freedom, which raise questions beyond those related to exploiting each modality separately. It is the aim of this paper to evoke and promote various challenges in multimodal data fusion at the conceptual level, without focusing on any specific model, method or application

Any-way and Sparse Analyses for Multimodal Fusion and Imaging Genomics

This dissertation aims to develop new algorithms that leverage sparsity and mutual information across data modalities built upon the independent component analysis (ICA) framework to improve the performance of current ICA-based multimodal fusion approaches. These algorithms are further applied to both simulated data and real neuroimaging and genomic data to examine their performance. The identified neuroimaging and genomic patterns can help better delineate the pathology of mental disorders or brain development. To alleviate the signal-background separation difficulties in infomax-decomposed sources for genomic data, we propose a sparse infomax by enhancing a robust sparsity measure, the Hoyer index. Hoyer index is scale-invariant and well suited for ICA frameworks since the scale of decomposed sources is arbitrary. Simulation results demonstrate that sparse infomax increases the component detection accuracy for situations where the source signal-to-background (SBR) ratio is low, particularly for single nucleotide polymorphism (SNP) data. The proposed sparse infomax is further extended into two data modalities as a sparse parallel ICA for applications to imaging genomics in order to investigate the associations between brain imaging and genomics. Simulation results show that sparse parallel ICA outperforms parallel ICA with improved accuracy for structural magnetic resonance imaging (sMRI)-SNP association detection and component spatial map recovery, as well as with enhanced sparsity for sMRI and SNP components under noisy cases. Applying the proposed sparse parallel ICA to fuse the whole-brain sMRI and whole-genome SNP data of 24985 participants in the UK biobank, we identify three stable and replicable sMRI-SNP pairs. The identified sMRI components highlight frontal, parietal, and temporal regions and associate with multiple cognitive measures (with different association strengths in different age groups for the temporal component). Top SNPs in the identified SNP factor are enriched in inflammatory disease and inflammatory response pathways, which also regulate gene expression, isoform percentage, transcription expression, or methylation level in the frontal region, and the regulation effects are significantly enriched. Applying the proposed sparse parallel ICA to imaging genomics in attention-deficit/hyperactivity disorder (ADHD), we identify and replicate one SNP component related to gray matter volume (GMV) alterations in superior and middle frontal gyri underlying working memory deficit in adults and adolescents with ADHD. The association is more significant in ADHD families than controls and stronger in adults and older adolescents than younger ones. The identified SNP component highlights SNPs in long non-coding RNAs (lncRNAs) in chromosome 5 and in several protein-coding genes that are involved in ADHD, such as MEF2C, CADM2, and CADPS2. Top SNPs are enriched in human brain neuron cells and regulate gene expression, isoform percentage, transcription expression, or methylation level in the frontal region. Moreover, to increase the flexibility and robustness in mining multimodal data, we propose aNy-way ICA, which optimizes the entire correlation structure of linked components across any number of modalities via the Gaussian independent vector analysis and simultaneously optimizes independence via separate (parallel) ICAs. Simulation results demonstrate that aNy-way ICA recover sources and loadings, as well as the true covariance patterns with improved accuracy compared to existing multimodal fusion approaches, especially under noisy conditions. Applying the proposed aNy-way ICA to integrate structural MRI, fractal n-back, and emotion identification task functional MRIs collected in the Philadelphia Neurodevelopmental Cohort (PNC), we identify and replicate one linked GMV-threat-2-back component, and the threat and 2-back components are related to intelligence quotient (IQ) score in both discovery and replication samples. Lastly, we extend the proposed aNy-way ICA with a reference constraint to enable prior-guided multimodal fusion. Simulation results show that aNy-way ICA with reference recovers the designed linkages between reference and modalities, cross-modality correlations, as well as loading and component matrices with improved accuracy compared to multi-site canonical correlation analysis with reference (MCCAR)+joint ICA under noisy conditions. Applying aNy-way ICA with reference to supervise structural MRI, fractal n-back, and emotion identification task functional MRIs fusion in PNC with IQ as the reference, we identify and replicate one IQ-related GMV-threat-2-back component, and this component is significantly correlated across modalities in both discovery and replication samples.Ph.D

Fronto-parietal homotopy in resting-state functional connectivity predicts task-switching performance

Homotopic functional connectivity reflects the degree of synchrony in spontaneous activity between homologous voxels in the two hemispheres. Previous studies have associated increased brain homotopy and decreased white matter integrity with performance decrements on different cognitive tasks across the life-span. Here, we correlated functional homotopy, both at the whole-brain level and specifically in fronto-parietal network nodes, with task-switching performance in young adults. Cue-to-target intervals (CTI: 300 vs. 1200 ms) were manipulated on a trial-by-trial basis to modulate cognitive demands and strategic control. We found that mixing costs, a measure of task-set maintenance and monitoring, were significantly correlated to homotopy in different nodes of the fronto-parietal network depending on CTI. In particular, mixing costs for short CTI trials were smaller with lower homotopy in the superior frontal gyrus, whereas mixing costs for long CTI trials were smaller with lower homotopy in the supramarginal gyrus. These results were specific to the fronto-parietal network, as similar voxel-wise analyses within a control language network did not yield significant correlations with behavior. These findings extend previous literature on the relationship between homotopy and cognitive performance to task-switching, and show a dissociable role of homotopy in different fronto-parietal nodes depending on task-demands

Multi-feature computational framework for combined signatures of dementia in underrepresented settings

Objetivo. El diagnóstico diferencial de la variante conductual de la demencia frontotemporal (bvFTD) y La enfermedad de Alzheimer (EA) sigue siendo un desafío en grupos subrepresentados y subdiagnosticados, incluidos los latinos, ya que los biomarcadores avanzados rara vez están disponibles. Directrices recientes para el estudio de demencia destacan el papel fundamental de los biomarcadores. Por lo tanto, nuevos complementarios rentables Se requieren enfoques en entornos clínicos. Acercarse. Desarrollamos un marco novedoso basado en un clasificador de aprendizaje automático que aumenta el gradiente, ajustado por la optimización bayesiana, en una función múltiple enfoque multimodal (que combina imágenes demográficas, neuropsicológicas y de resonancia magnética) (IRM) y electroencefalografía/datos de conectividad de IRM funcional) para caracterizar neurodegeneración utilizando la armonización del sitio y la selección de características secuenciales. Evaluamos 54 DFTvc y 76 pacientes con EA y 152 controles sanos (HC) de un consorcio latinoamericano (ReDLat). Resultados principales. El modelo multimodal arrojó una alta clasificación de área bajo la curva (pacientes con DFTvc frente a HC: 0,93 (±0,01); pacientes con EA frente a HC: 0,95 (±0,01); DFTvv frente a EA pacientes: 0,92 (±0,01)). El enfoque de selección de características filtró con éxito información no informativa marcadores multimodales (de miles a decenas). Resultados. Probado robusto contra multimodal heterogeneidad, variabilidad sociodemográfica y datos faltantes. Significado. El modelo con precisión subtipos de demencia identificados utilizando medidas fácilmente disponibles en entornos subrepresentados, con un rendimiento similar al de los biomarcadores avanzados. Este enfoque, si se confirma y replica, puede complementar potencialmente las evaluaciones clínicas en los países en desarrollo.Q1Q1Abstract Objective. The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings. Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat). Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens). Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data. Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries.https://orcid.org/0000-0001-6529-7077https://scholar.google.com/citations?hl=es&user=kaGongoAAAAJ&view_op=list_works&sortby=pubdatehttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000055000Revista Internacional - IndexadaS

Exploring the Electrophysiological Correlates of the Default-Mode Network with Intracerebral EEG

While functional imaging studies allow for a precise spatial characterization of resting state networks, their neural correlates and thereby their fine-scale temporal dynamics remain elusive. A full understanding of the mechanisms at play requires input from electrophysiological studies. Here, we discuss human and non-human primate electrophysiological data that explore the neural correlates of the default-mode network. Beyond the promising findings obtained with non-invasive approaches, emerging evidence suggests that invasive recordings in humans will be crucial in order to elucidate the neural correlates of the brain's default-mode function. In particular, we contend that stereotactic-electroencephalography, which consists of implanting multiple depth electrodes for pre-surgical evaluation in drug-resistant epilepsy, is particularly suited for this endeavor. We support this view by providing rare data from depth recordings in human posterior cingulate cortex and medial prefrontal cortex that show transient neural deactivation during task-engagement

The neurobiology of cortical music representations

Music is undeniable one of humanity’s defining traits, as it has been documented since the earliest days of mankind, is present in all knowcultures and perceivable by all humans nearly alike. Intrigued by its omnipresence, researchers of all disciplines started the investigation of music’s mystical relationship and tremendous significance to humankind already several hundred years ago. Since comparably recently, the immense advancement of neuroscientific methods also enabled the examination of cognitive processes related to the processing of music. Within this neuroscience ofmusic, the vast majority of research work focused on how music, as an auditory stimulus, reaches the brain and howit is initially processed, aswell as on the tremendous effects it has on and can evoke through the human brain. However, intermediate steps, that is how the human brain achieves a transformation of incoming signals to a seemingly specialized and abstract representation of music have received less attention. Aiming to address this gap, the here presented thesis targeted these transformations, their possibly underlying processes and how both could potentially be explained through computational models. To this end, four projects were conducted. The first two comprised the creation and implementation of two open source toolboxes to first, tackle problems inherent to auditory neuroscience, thus also affecting neuroscientific music research and second, provide the basis for further advancements through standardization and automation. More precisely, this entailed deteriorated hearing thresholds and abilities in MRI settings and the aggravated localization and parcellation of the human auditory cortex as the core structure involved in auditory processing. The third project focused on the human’s brain apparent tuning to music by investigating functional and organizational principles of the auditory cortex and network with regard to the processing of different auditory categories of comparable social importance, more precisely if the perception of music evokes a is distinct and specialized pattern. In order to provide an in depth characterization of the respective patterns, both the segregation and integration of auditory cortex regions was examined. In the fourth and final project, a highly multimodal approach that included fMRI, EEG, behavior and models of varying complexity was utilized to evaluate how the aforementioned music representations are generated along the cortical hierarchy of auditory processing and how they are influenced by bottom-up and top-down processes. The results of project 1 and 2 demonstrated the necessity for the further advancement of MRI settings and definition of working models of the auditory cortex, as hearing thresholds and abilities seem to vary as a function of the used data acquisition protocol and the localization and parcellation of the human auditory cortex diverges drastically based on the approach it is based one. Project 3 revealed that the human brain apparently is indeed tuned for music by means of a specialized representation, as it evoked a bilateral network with a right hemispheric weight that was not observed for the other included categories. The result of this specialized and hierarchical recruitment of anterior and posterior auditory cortex regions was an abstract music component ix x SUMMARY that is situated in anterior regions of the superior temporal gyrus and preferably encodes music, regardless of sung or instrumental. The outcomes of project 4 indicated that even though the entire auditory cortex, again with a right hemispheric weight, is involved in the complex processing of music in particular, anterior regions yielded an abstract representation that varied excessively over time and could not sufficiently explained by any of the tested models. The specialized and abstract properties of this representation was furthermore underlined by the predictive ability of the tested models, as models that were either based on high level features such as behavioral representations and concepts or complex acoustic features always outperformed models based on single or simpler acoustic features. Additionally, factors know to influence auditory and thus music processing, like musical training apparently did not alter the observed representations. Together, the results of the projects suggest that the specialized and stable cortical representation of music is the outcome of sophisticated transformations of incoming sound signals along the cortical hierarchy of auditory processing that generate a music component in anterior regions of the superior temporal gyrus by means of top-down processes that interact with acoustic features, guiding their processing.Musik ist unbestreitbarer Weise eine der definierenden Eigenschaften des Menschen. Dokumentiert seit den frühesten Tagen der Menschheit und in allen bekannten Kulturen vorhanden, ist sie von allenMenschen nahezu gleichwahrnehmbar. Fasziniert von ihrerOmnipräsenz haben Wissenschaftler aller Disziplinen vor einigen hundert Jahren begonnen die mystische Beziehung zwischen Musik und Mensch, sowie ihre enorme Bedeutung für selbigen zu untersuchen. Seit einem vergleichsweise kurzem Zeitraum ist es durch den immensen Fortschritt neurowissenschafticher Methoden auch möglich die kognitiven Prozesse, welche an der Verarbeitung von Musik beteiligt, sind zu untersuchen. Innerhalb dieser Neurowissenschaft der Musik hat sich ein Großteil der Forschungsarbeit darauf konzentriert wie Musik, als auditorischer Stimulus, das menschliche Gehirn erreicht und wie sie initial verarbeitet wird, als auch welche kolossallen Effekte sie auf selbiges hat und auch dadurch bewirken kann. Jedoch haben die Zwischenschritte, also wie das menschliche Gehirn eintreffende Signale in eine scheinbar spezialisierte und abstrakte Repräsentation vonMusik umwandelt, vergleichsweise wenig Aufmerksamkeit erhalten. Um die dadurch entstandene Lücke zu adressieren, hat die hier vorliegende Dissertation diese Prozesse und wie selbige durch Modelle erklärt werden können in vier Projekten untersucht. Die ersten beiden Projekte beinhalteten die Herstellung und Implementierung von zwei Toolboxen um erstens, inhärente Probleme der auditorischen Neurowissenschaft, daher auch neurowissenschaftlicher Untersuchungen von Musik, zu verbessern und zweitens, eine Basis für weitere Fortschritte durch Standardisierung und Automatisierung zu schaffen. Im genaueren umfasste dies die stark beeinträchtigten Hörschwellen und –fähigkeiten in MRT-Untersuchungen und die erschwerte Lokalisation und Parzellierung des menschlichen auditorischen Kortex als Kernstruktur auditiver Verarbeitung. Das dritte Projekt befasste sich mit der augenscheinlichen Spezialisierung von Musik im menschlichen Gehirn durch die Untersuchung funktionaler und organisatorischer Prinzipien des auditorischen Kortex und Netzwerks bezüglich der Verarbeitung verschiedener auditorischer Kategorien vergleichbarer sozialer Bedeutung, im genaueren ob die Wahrnehmung von Musik ein distinktes und spezialisiertes neuronalenMuster hervorruft. Umeine ausführliche Charakterisierung der entsprechenden neuronalen Muster zu ermöglichen wurde die Segregation und Integration der Regionen des auditorischen Kortex untersucht. Im vierten und letzten Projekt wurde ein hochmultimodaler Ansatz,welcher fMRT, EEG, Verhalten undModelle verschiedener Komplexität beinhaltete, genutzt, umzu evaluieren, wie die zuvor genannten Repräsentationen von Musik entlang der kortikalen Hierarchie der auditorischen Verarbeitung generiert und wie sie möglicherweise durch Bottom-up- und Top-down-Ansätze beeinflusst werden. Die Ergebnisse von Projekt 1 und 2 demonstrierten die Notwendigkeit für weitere Verbesserungen von MRTUntersuchungen und die Definition eines Funktionsmodells des auditorischen Kortex, daHörxi xii ZUSAMMENFASSUNG schwellen und –fähigkeiten stark in Abhängigkeit der verwendeten Datenerwerbsprotokolle variierten und die Lokalisation, sowie Parzellierung des menschlichen auditorischen Kortex basierend auf den zugrundeliegenden Ansätzen drastisch divergiert. Projekt 3 zeigte, dass das menschliche Gehirn tatsächlich eine spezialisierte Repräsentation vonMusik enthält, da selbige als einzige auditorische Kategorie ein bilaterales Netzwerk mit rechtshemisphärischer Gewichtung evozierte. Aus diesemNetzwerk, welches die Rekrutierung anteriorer und posteriorer Teile des auditorischen Kortex beinhaltete, resultierte eine scheinbar abstrakte Repräsentation von Musik in anterioren Regionen des Gyrus temporalis superior, welche präferiert Musik enkodiert, ungeachtet ob gesungen oder instrumental. Die Resultate von Projekt 4 deuten darauf hin, dass der gesamte auditorische Kortex, erneut mit rechtshemisphärischer Gewichtung, an der komplexen Verarbeitung vonMusik beteiligt ist, besonders aber anteriore Regionen, die bereits genannten abstrakte Repräsentation hervorrufen, welche sich exzessiv über die Zeitdauer derWahrnehmung verändert und nicht hinreichend durch eines der getestetenModelle erklärt werden kann. Die spezialisierten und abstrakten Eigenschaften dieser Repräsentationen wurden weiterhin durch die prädiktiven Fähigkeiten der getestetenModelle unterstrichen, daModelle, welche entweder auf höheren Eigenschaften wie Verhaltensrepräsentationen und mentalen Konzepten oder komplexen akustischen Eigenschaften basierten, stets Modelle, welche auf niederen Attributen wie simplen akustischen Eigenschaften basierten, übertrafen. Zusätzlich konnte kein Effekt von Faktoren, wie z.B. musikalisches Training, welche bekanntermaßen auditorische und daherMusikverarbeitung beeinflussen, nachgewiesen werden. Zusammengefasst deuten die Ergebnisse der Projekte darauf, hin dass die spezialisierte und stabile kortikale Repräsentation vonMusik ein Resultat komplexer Prozesse ist, welche eintreffende Signale entlang der kortikalen Hierarchie auditorischer Verarbeitung in eine abstrakte Repräsentation vonMusik innerhalb anteriorer Regionen des Gyrus temporalis superior durch Top-Down-Prozesse, welche mit akustischen Eigenschaften interagieren und deren Verarbeitung steuern, umwandeln